Project 1 will determine the consequences of parathyroid hormone-related protein (PTHrP) over-expression in theproximal convoluted tubules of transgenic mice. A unique transgene construct employing the gamma-GT promoter-I will allow for control over the timing of transgene activation, thus permitting an evaluation of the roles played by PTHrPs in developmental renal biology and in adult tubular physiology. The phenotype that results from renal tubular PTHrP over-expression will guide further studies to better define the physiologic role of PTHrP in the proximal tubule. Project 2 will characterize the effects of PTHrP on renal mesangial cell biology. The project will focus on the effects of PTHrP on mesangial cell proliferation, matrix production, and contractile properties. PTHrP is a widely expressed, highly conserved peptide which influences mitogenesis and differentiation in several different tissues. Appreciating its physiological role in the kidney will lead to greater understanding of the complex control of glomerular and tubular growth, differentiation, and response to injury.